Epzicom Information
Epzicom (Abacavir sulfate,lamivudine) Description
Epzicom (Abacavir sulfate,lamivudine) Tablets contain the following 2 synthetic nucleoside analogues: abacavir sulfate (ZIAGEN, also a component of TRIZIVIR) and lamivudine (also known as EPIVIR or 3TC) with inhibitory activity against HIV-1.
Epzicom (Abacavir sulfate,lamivudine) Tablets are for oral administration. Each orange, film-coated tablet contains the active ingredients 600 mg of abacavir as abacavir sulfate and 300 mg of lamivudine, and the inactive ingredients magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The tablets are coated with a film (OPADRY orange YS-1-13065-A) that is made of FD&C Yellow No. 6, hypromellose, polyethylene glycol 400, polysorbate 80, and titanium dioxide.
The chemical name of abacavir sulfate is 14-[2-amino-6-(cyclopropylamino)-9-purin-9-yl]-2-cyclopentene-1-methanol sulfate (salt) (2:1). Abacavir sulfate is the enantiomer with , absolute configuration on the cyclopentene ring. It has a molecular formula of (CHNO)•HSO and a molecular weight of 670.76 daltons. It has the following structural formula:
Abacavir sulfate is a white to off-white solid with a solubility of approximately 77 mg/mL in distilled water at 25°C.
In vivo, abacavir sulfate dissociates to its free base, abacavir. All dosages for abacavir sulfate are expressed in terms of abacavir.
The chemical name of lamivudine is (2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one. Lamivudine is the (-)enantiomer of a dideoxy analogue of cytidine. Lamivudine has also been referred to as (-)2′,3′-dideoxy, 3′-thiacytidine. It has a molecular formula of CHNOS and a molecular weight of 229.3 daltons. It has the following structural formula:
Lamivudine is a white to off-white crystalline solid with a solubility of approximately 70 mg/mL in water at 20°C.
Epzicom (Abacavir sulfate,lamivudine) Microbiology
Abacavir is a carbocyclic synthetic nucleoside analogue. Abacavir is converted by cellular enzymes to the active metabolite, carbovir triphosphate (CBV-TP), an analogue of deoxyguanosine-5′-triphosphate (dGTP). CBV-TP inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA. The lack of a 3′-OH group in the incorporated nucleotide analogue prevents the formation of the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated. CBV-TP is a weak inhibitor of cellular DNA polymerases α, β, and γ.
Lamivudine is a synthetic nucleoside analogue. Intracellularly lamivudine is phosphorylated to its active 5′-triphosphate metabolite, lamivudine triphosphate (3TC-TP). The principal mode of action of 3TC-TP is inhibition of RT via DNA chain termination after incorporation of the nucleotide analogue. CBV-TP and 3TC-TP are weak inhibitors of cellular DNA polymerases α, β, and γ.
HIV-1 isolates with reduced susceptibility to the combination of abacavir and lamivudine have been selected in cell culture and have also been obtained from patients failing abacavir/lamivudine-containing regimens. Genotypic characterization of abacavir/lamivudine-resistant viruses selected in cell culture identified amino acid substitutions M184V/I, K65R, L74V, and Y115F in HIV-1 RT.
Genotypic analysis of isolates selected in cell culture and recovered from abacavir-treated patients demonstrated that amino acid substitutions K65R, L74V, Y115F, and M184V/I in HIV-1 RT contributed to abacavir resistance. Genotypic analysis of isolates selected in cell culture and recovered from lamivudine-treated patients showed that the resistance was due to a specific amino acid substitution in HIV-1 RT at codon 184 changing the methionine to either isoleucine or valine (M184V/I). In a study of therapy-naive adults receiving ZIAGEN 600 mg once daily (n = 384) or 300 mg twice daily (n = 386) in a background regimen of lamivudine 300 mg and efavirenz 600 mg once daily (Study CNA30021), the incidence of virologic failure at 48 weeks was similar between the 2 groups (11% in both arms). Genotypic (n = 38) and phenotypic analyses (n = 35) of virologic failure isolates from this study showed that the RT substitutions that emerged during abacavir/lamivudine once-daily and twice-daily therapy were K65R, L74V, Y115F, and M184V/I. The abacavir- and lamivudine-associated resistance substitution M184V/I was the most commonly observed substitution in virologic failure isolates from patients receiving abacavir/lamivudine once daily (56%, 10/18) and twice daily (40%, 8/20).
Thirty-nine percent (7/18) of the isolates from patients who experienced virologic failure in the abacavir once-daily arm had a >2.5-fold decrease in abacavir susceptibility with a median-fold decrease of 1.3 (range: 0.5 to 11) compared with 29% (5/17) of the failure isolates in the twice-daily arm with a median-fold decrease of 0.92 (range: 0.7 to 13). Fifty-six percent (10/18) of the virologic failure isolates in the once-daily abacavir group compared with 41% (7/17) of the failure isolates in the twice-daily abacavir group had a >2.5-fold decrease in lamivudine susceptibility with median-fold changes of 81 (range 0.79 to >116) and 1.1 (range 0.68 to >116) in the once-daily and twice-daily abacavir arms, respectively.
Cross-resistance has been observed among NRTIs. Viruses containing abacavir and lamivudine resistance-associated amino acid substitutions, namely, K65R, L74V, M184V, and Y115F, exhibit cross-resistance to didanosine, emtricitabine, lamivudine, tenofovir, and zalcitabine in cell culture and in patients. The K65R substitution can confer resistance to abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, and zalcitabine; the L74V substitution can confer resistance to abacavir, didanosine, and zalcitabine; and the M184V substitution can confer resistance to abacavir, didanosine, emtricitabine, lamivudine, and zalcitabine.
The combination of abacavir/lamivudine has demonstrated decreased susceptibility to viruses with the substitutions K65R with or without the M184V/I substitution, viruses with L74V plus the M184V/I substitution, and viruses with thymidine analog mutations (TAMs: M41L, D67N, K70R, L210W, T215Y/F, K219 E/R/H/Q/N) plus M184V. An increasing number of TAMs is associated with a progressive reduction in abacavir susceptibility.
Epzicom (Abacavir sulfate,lamivudine) Indications And Usage
Epzicom (Abacavir sulfate,lamivudine) Tablets, in combination with other antiretroviral agents, are indicated for the treatment of HIV-1 infection.
Additional important information on the use of Epzicom (Abacavir sulfate,lamivudine) for treatment of HIV-1 infection:
See WARNINGS, ADVERSE REACTIONS, and Description of Clinical Studies.
Epzicom (Abacavir sulfate,lamivudine) Contraindications
Epzicom (Abacavir sulfate,lamivudine) Tablets are contraindicated in patients with hepatic impairment (see CLINICAL PHARMACOLOGY).
Epzicom (Abacavir sulfate,lamivudine) Warnings
Serious and sometimes fatal hypersensitivity reactions have been associated with Epzicom (Abacavir sulfate,lamivudine) and other abacavir-containing products.
Epzicom (Abacavir sulfate,lamivudine) contains fixed doses of 2 nucleoside analogues, abacavir and lamivudine, and should not be administered concomitantly with other abacavir-containing and/or lamivudine-containing products (ZIAGEN, EPIVIR, COMBIVIR, or TRIZIVIR).
The complete prescribing information for all agents being considered for use with Epzicom (Abacavir sulfate,lamivudine) should be consulted before combination therapy with Epzicom (Abacavir sulfate,lamivudine) is initiated.
Epzicom (Abacavir sulfate,lamivudine) Precautions
In a published prospective, observational, epidemiological study designed to investigate the rate of myocardial infarction in patients on combination antiretroviral therapy, the use of abacavir within the previous 6 months was correlated with an increased risk of myocardial infarction (MI). In a sponsor-conducted pooled analysis of clinical trials, no excess risk of MI was observed in abacavir-treated subjects as compared with control subjects. In totality, the available data from the observational cohort and from clinical trials are inconclusive.
As a precaution, the underlying risk of coronary heart disease should be considered when prescribing antiretroviral therapies, including abacavir, and action taken to minimize all modifiable risk factors (e.g., hypertension, hyperlipidemia, diabetes mellitus, and smoking).
The Centers for Disease Control and Prevention recommend that HIV-1-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection.
Epzicom (Abacavir sulfate,lamivudine) Adverse Reactions
Laboratory abnormalities observed in clinical studies of ZIAGEN were anemia, neutropenia, liver function test abnormalities, and elevations of CPK, blood glucose, and triglycerides. Additional laboratory abnormalities observed in clinical studies of EPIVIR were thrombocytopenia and elevated levels of bilirubin, amylase, and lipase.
The frequencies of treatment-emergent laboratory abnormalities were comparable between treatment groups in Study CNA30021.
Epzicom (Abacavir sulfate,lamivudine) Dosage And Administration
The recommended oral dose of Epzicom (Abacavir sulfate,lamivudine) for adults is one tablet daily, in combination with other antiretroviral agents (see INDICATIONS AND USAGE: Description of Clinical Studies, PRECAUTIONS, MICROBIOLOGY, and CLINICAL PHARMACOLOGY).
Epzicom (Abacavir sulfate,lamivudine) can be taken with or without food.
Epzicom (Abacavir sulfate,lamivudine) How Supplied
Epzicom (Abacavir sulfate,lamivudine) is available as tablets. Each tablet contains 600 mg of abacavir as abacavir sulfate and 300 mg of lamivudine. The tablets are orange, film-coated, modified capsule-shaped, and debossed with GS FC2 on one side with no markings on the reverse side. They are packaged as follows:
Bottles of 30 Tablets (NDC 0173-0742-00).
Epzicom (Abacavir sulfate,lamivudine) Animal Toxicology
Myocardial degeneration was found in mice and rats following administration of abacavir for 2 years. The systemic exposures were equivalent to 7 to 24 times the expected systemic exposure in humans. The clinical relevance of this finding has not been determined.
Epzicom (Abacavir sulfate,lamivudine) Medication Guide
Read the Medication Guide that comes with Epzicom (Abacavir sulfate,lamivudine) before you start taking it and each time you get a refill because there may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment. Be sure to carry your Epzicom (Abacavir sulfate,lamivudine) Warning Card with you at all times.
A list of these symptoms is on the Warning Card your pharmacist gives you. Carry this Warning Card with you.
Epzicom (Abacavir sulfate,lamivudine) can have other serious side effects. Be sure to read the section below entitled "What are the possible side effects of Epzicom (Abacavir sulfate,lamivudine) ?"
Epzicom (Abacavir sulfate,lamivudine) is a prescription medicine used to treat HIV infection. Epzicom (Abacavir sulfate,lamivudine) includes 2 medicines: abacavir (ZIAGEN) and lamivudine or 3TC (EPIVIR). See the end of this Medication Guide for a complete list of ingredients in Epzicom (Abacavir sulfate,lamivudine) . Both of these medicines are called nucleoside analogue reverse transcriptase inhibitors (NRTIs). When used together, they help lower the amount of HIV in your blood. This helps to keep your immune system as healthy as possible so that it can help fight infection.
Different combinations of medicines are used to treat HIV infection. You and your doctor should discuss which combination of medicines is best for you.
Some HIV medicines including Epzicom (Abacavir sulfate,lamivudine) may increase your risk of heart attack. If you have heart problems, smoke, or suffer from diseases that increase your risk of heart disease such as high blood pressure, high cholesterol, or diabetes, tell your doctor.
The most common side effects with Epzicom (Abacavir sulfate,lamivudine) are trouble sleeping, depression, headache, tiredness, dizziness, nausea, diarrhea, rash, fever, stomach pain, abnormal dreams, and anxiety. Most of these side effects did not cause people to stop taking Epzicom (Abacavir sulfate,lamivudine) .
This list of side effects is not complete. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Medicines are sometimes prescribed for conditions that are not mentioned in Medication Guides. Do not use Epzicom (Abacavir sulfate,lamivudine) for a condition for which it was not prescribed. Do not give Epzicom (Abacavir sulfate,lamivudine) to other people, even if they have the same symptoms that you have. It may harm them.
This Medication Guide summarizes the most important information about Epzicom (Abacavir sulfate,lamivudine) . If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for the information that is written for healthcare professionals or call 1-888-825-5249.
March 2009EPZ:2MG
COMBIVIR, EPIVIR, Epzicom (Abacavir sulfate,lamivudine) , TRIZIVIR, and ZIAGEN are registered trademarks of GlaxoSmithKline.
* The brands listed are trademarks of their respective owners and are not trademarks of GlaxoSmithKline. The makers of these brands are not affiliated with and do not endorse GlaxoSmithKline or its products.
GlaxoSmithKlineResearch Triangle Park, NC 27709
Lamivudine is manufactured under agreement from Basingstoke, UK
©2009, GlaxoSmithKline. All rights reserved.
March 2009EPZ:2PI
Epzicom (Abacavir sulfate,lamivudine)
